Degenerative joint disease is a slowly progressive destructive disease of the joints which is widespread in man and other species. The underlying cause or causes of osteoarthritis have not been identified despite numerous histological, biochemical and biomechanical studies examining the changes that occur as the disease develops. The earliest recognizable biochemical signs reported include changes in the amount, molecular size, extractibility and aggregation of the proteoglycans isolated from articular cartilage in osteoarthritis. In this proposal, the STR/IN mouse, which spontaneously develops osteoarthritis, will be used as an animal model to investigate the biochemical changes that occur in degenerative joint disease. This animal model has the advantage that the development of the disease can be studied in many animals, in a short time period, without the need for surgical procedures. Mouse articular cartilage will be radiolabelled in vivo with 35SO4 and the biochemical characteristics of the newly synthesized proteoglycans examined. The characteristics of the endogenous mouse articular cartilage proteoglycans will be determined after labelling the extracted proteoglycans with 25I-iodine in vitro. Analyses of proteoglycan from age- and sex-matched STR/IN mice will be compared with those from a related non-osteoarthritic strain (STR/N). The biochemical results will be complemented by data from transmission electron microscopy of the cartilage proteoglycans extracted from both mouse strains. Furthermore, radioimmunoassay and immunohistochemical procedures will be used to quantitate and identify specific proteoglycan structures and link protein in the articular cartilage of STR/IN and STR/N mice. Changes observed in the structure of mouse articular cartilage proteoglycan in osteoarthritis will be compared to those in human osteoarthritic cartilage.